1lqh

Overview
Scorpion toxins are 61- to 76-residue long proteins that modulate the gating properties of voltage-gated sodium channels. According to their mode of action and binding properties,scorpion toxins are divided into two major classes, alpha- and beta- toxins. LqhαIT is a 64-residue scorpion α-toxin from Leiurus quinquestriatus hebraeus (yellow scorpion) venom. Scorpion α-toxins prolong the action potential by inhibiting channel inactivation. The binding site of scorpion α-neurotoxins on voltage-gated sodium channels is named neurotoxin receptor site-3. Scorpion α-toxins are similar in structure and exhibit a similar mode of action, but are very diverse in sequence and selectivity. Some scorpion α-neurotoxins show specificity for insect sodium channels and others are specific for mammalian sodium channels and exhibit different affinities to sodium channel subtypes in mammalian neurons. LqhαIT is the most insecticidal among scorpion α-toxins.

About this Structure
The structure of LqhαIT was solved by NMR (1) and was found to resemble that of other scorpion toxins: a core composed of an α-helix packed against a three stranded anti-parallel β-sheet and stabilized by four disulfide bonds.

The Binding-Site
Mutational studies identified residues Lys8, Tyr10, Phe17, Arg18, Trp38, Asn44 and the C- tail region (Ile57, Arg58, Val59, Lys62 and Arg64) of LqhαIT as important for the interaction with sodium channels (2). NMR studies of LqhαIT with a peptide derived from part of neurotoxin receptor site-3 (D4S3-S4) identified residues Lys8, Asn9, Cys12, Val13, Arg18, Trp38, Ala39 and Arg58 of LqhαIT as participating in binding to that extra-cellular part of the sodium channel (3). Both methods led to the identification of two regions on the surface of LqhαIT that participate in binding of the toxin to neurotoxin receptor site-3 on sodium channels.